This proposal is designed to study the molecular, cellular and animal pharmacology of 5-azadeoxycytidine in order to evaluate, preclinically, the antileukemic potential of this analog. Biochemical studies concerning the enzymatic phosphorylation and deamination of 5-azadeoxycytidine will be performed. The 5'-triphosphate nucleotide form of 5-azadeoxycytidine will be synthesized enzymatically and the effect of this deoxynucleotide analog on DNA dependent DNA polymerase reaction will be investigated. The cell cycle specificity of 5-azadeoxycytidine and its effect on cell cycle progression will be studied. The effect of 5-azadeoxycytidine on cellular macromolecular synthesis and deoxynucleotide metabolism will be determined. The biochemical and cellular data on 5-azadeoxycytidine will be used to design optimal dose schedules for this agent based on scientific rationale that will be put to test in mice with L1210 leukemia. The metabolism and toxicology of 5-azadeoxycytidine will be investigated.